Karen Petersen

Increased Disease Burden and Antibiotic Resistance of Bacteria Causing Severe Community-Acquired Lower Respiratory Tract Infections in Human Immunodeficiency Virus Type 1-Infected Children

To improve the management of lower respiratory tract infections (LRTI) in human immunodeficiency virus type 1 (HIV-1)-infected children, we assessed the burden of disease, clinical outcome and antibiotic susceptibility of bacteria causing severe community-acquired LRTI in children. A prospective, descriptive study was performed in the pediatric wards at a secondary and tertiary care hospital in South Africa. Urban black children aged 2-60 months admitted with severe acute LRTI from March 1997 through February 1998 were enrolled. HIV-1 infection was present in 45.1% of 1215 cases of severe LRTI. Bacteremia occurred in 14.9% of HIV-1-infected and in 6.5% of HIV-1-uninfected children (P<.00001). The estimated relative incidence of bacteremic severe LRTI in children aged from 2 to 24 months were greater in HIV-1-infected than in -uninfected children for Streptococcus pneumoniae (risk ratio [RR], 42.9; 95% confidence interval [CI], 20.7-90.2), Haemophilus influenzae type b (RR, 21.4; 95% CI, 9.4-48.4), Staphylococcus aureus (RR, 97.9; 95% CI, 11.4-838.2) and Escherichia coli (RR, 49.0; 95% CI, 15.4-156). Isolation of Mycobacterium tuberculosis was also more common in HIV-1-infected than in -uninfected children (RR, 22.5; 95% CI, 13.4-37.6). In HIV-1-infected children, 60% of S. aureus and 85.7% of E. coli isolates were resistant to methicillin and trimethoprim-sulfamethoxazole, respectively. The case-fatality rates among HIV-1-infected children was 13.1%, and among HIV-1-uninfected children, 2.1% (adjusted odds ratio [AOR]; 6.52, 95% CI, 3.53-12.05; P<.00001). The changing spectrum of bacteria and antibiotic susceptibility patterns in HIV-1-infected children requires a reevaluation of the empirical treatment of community-acquired severe LRTI in children from developing countries with a high prevalence of childhood HIV-1 infection.

Impact of human immunodeficiency virus type 1 on the disease spectrum of Streptococcus pneumoniae in South African children.

Background. HIV-infected children are at increased risk of developing invasive Streptococcus pneumoniae disease. Objective. To determine the impact of the HIV epidemic on the epidemiology of invasive pneumococcal disease in hospitalized African children. Methods. Children <12 years of age with invasive pneumococcal disease were enrolled between March, 1997, and February, 1999. Results. The seroprevalence of HIV was 64.9% (146 of 225). In children with pneumococcal isolates from serogroups 6, 9, 14, 19 or 23 (pediatric serogroups), pneumonia and pneumonia with concurrent meningitis was more common in HIV-infected children (P = 0.03 and P = 0.003, respectively), whereas septic shock occurred more often in HIV-uninfected children (P = 0.0003). The overall burden of severe invasive pneumococcal disease was 41.7 (95% confidence interval, 26.5 to 65.6) fold increased in HIV-infected compared with HIV-uninfected children. Reduced susceptibility to penicillin (45.9%vs. 27.9%, P = 0.009), trimethoprim-sulfamethoxazole (44.5%vs. 19.0%, P = 0.0002) and multiple drug resistance was more common in HIV-infected than in HIV-uninfected children (24.0%vs. 6.4%, P = 0.01), respectively. The increased burden of disease and reduced antibiotic susceptibility of pneumococcal isolates in HIV-infected children was because of a heightened susceptibility to disease caused by pediatric serogroups in these children than in HIV-uninfected children (P = 0.01). Although the case fatality rates did not differ between HIV-infected and -uninfected children, mortality in HIV-infected children with advanced AIDS (Stage C, 22 of 61; 36.1%) was greater than that in children with moderate AIDS (Stage B, 12 of 85; 14.1%, P = 0.002). Conclusions. In children with invasive pneumococcal disease caused by the pediatric serogroups, HIV-infected children have more antibiotic-resistant isolates and have a different clinical presentation than do HIV-uninfected children.

Reduced effectiveness of Haemophilus influenzae type b conjugate vaccine in children with a high prevalence of human immunodeficiency virus type 1 infection

Background. Haemophilus influenzae type b (Hib) conjugate vaccines have successfully reduced the burden of invasive Hib disease in developed countries; however, their effectiveness in countries with a high incidence of pediatric HIV-1 is unknown. Methods. The effectiveness of Hib conjugate vaccine was prospectively evaluated in South African children. The burden of invasive Hib disease in children <1 year old was compared in 2 cohorts. The first cohort included 22 000 African children born in 1997 [969 (4.45%) of whom were estimated to be HIV-1-infected] who were not vaccinated with Hib conjugate vaccine. This group was compared with 19 267 children [1162 (6.03%) of whom were estimated to be HIV-1-infected] vaccinated at 6, 10 and 14 weeks of age with an Hib conjugate vaccine [TETRAMUNE (polyribosylribitol phosphate-CRM197-diphtheria-tetanus toxoids-whole cell pertussis)] between March, 1998, and June, 1999. Results. The estimated burden of invasive Hib disease in nonimmunized HIV-1-infected children <1 year of age was 5.9-fold [95% confidence interval (95% CI), 2.7 to 12.6] higher than in HIV-1-uninfected children. The overall estimated effectiveness of Hib conjugate vaccine in fully vaccinated children <1 year of age was 83.2% (95% CI 60.3 to 92.9). Vaccine effectiveness was significantly reduced in HIV-1- infected [43.9% (95% CI −76.1 to 82.1)] compared with uninfected children [96.5% (95% CI 74.4 to 99.5);P < 10−5]. Among three of the fully vaccinated HIV-1-infected children who developed invasive Hib disease, the anti-Hib polyribosylribitol phosphate serum antibody concentrations were 0.23, 0.25 and 0.68 &mgr;g/ml. Conclusion. Although the Hib conjugate vaccine was less effective among HIV-1-infected than among uninfected children, it was 83% effective in preventing overall invasive Hib disease and therefore should be considered for inclusion in the routine vaccination schedule by other African countries.

Impact of human immunodeficiency virus type 1 infection on the epidemiology and outcome of bacterial Meningitis in South African children

OBJECTIVE To define the impact that the human immunodeficiency virus type 1 (HIV-1) epidemic has had on the burden and outcome of bacterial meningitis in an area with a high prevalence of pediatric HIV-1 infection. METHODS Children less than 12 years of age with proven or suspected bacterial meningitis were enrolled in this study between March 1997 and February 1999, and their hospital records were retrospectively reviewed for clinical data. RESULTS Sixty-two (42.2%) of the 147 children tested for HIV-1 infection were infected. Streptococcus pneumoniae (Pnc) exceeded Haemophilus influenzae type b (Hib) as the most important cause of meningitis in HIV-1-infected (74.2% vs. 12.9%, respectively) compared with uninfected children (29.4% vs. 42.3%, respectively, P less than 10(-5)). The estimated relative risk of Pnc meningitis was greater in HIV-1-infected than in uninfected children under 2 years of age (relative risk [RR] = 40.4; 95% confidence intervals [CI] = 17.7-92.2). Overall, HIV-1-infected children had a higher rate of mortality than uninfected children (30.6% vs. 11.8%, respectively, P = 0.01), and in particular, HIV-1-infected children with Pnc meningitis (60.8% vs. 36.0%, respectively, P = 0.04) had a poorer outcome. CONCLUSIONS Streptococcus pneumoniae has exceeded Hib as the most important pathogen causing bacterial meningitis in HIV-1-infected compared with uninfected children. Effective vaccination against Hib and Pnc should be evaluated to reduce the overall burden of bacterial meningitis in HIV-1-infected children.

Differing manifestations of respiratory syncytial virus-associated severe lower respiratory tract infections in human immunodeficiency virus type 1-infected and uninfected children.

BACKGROUND Respiratory syncytial virus (RSV) causes increased morbidity and mortality in immunocompromised children. The outcome of RSV-associated lower respiratory tract infections (LRTI) in HIV-infected children, is less well described. METHODS Children from a prospective study evaluating the etiology of

Immunogenicity of 13-valent pneumococcal conjugate vaccine among children with underlying medical conditions.

BACKGROUND Streptococcus pneumoniae is a leading cause of vaccine-preventable disease in children under 5years. Immunocompromised children and those with underlying diseases are at increased risk of severe complications from vaccine-preventable infections. We studied the humoral immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) in children with HIV-infection, kidney or lung disease and compared this to the response in healthy control children. METHODS Children aged 12-71months with underlying conditions including HIV-infection and those with kidney and lung diseases (at-risk children), and a healthy control group were vaccinated with PCV13. The at-risk children received two doses of PCV13 and the controls received one dose. Serotype-specific antibodies for all PCV13 serotypes were measured by a luminex-based enzyme immunoassay at baseline and post-vaccination. RESULTS After the first PCV13 dose, the fold-increase in serotype-specific antibody geometric mean concentrations (GMCs) from baseline and the percentage of participants with ≥4-fold-increase in antibody concentrations was similar between the control and at-risk children. GMCs were, however, lower for three of the 13 serotypes in HIV-infected children, higher for serotype 6B in children with kidney disease and higher for serotypes 6B and 14 in children with lung disease. After second vaccine dose HIV-infected children had an increase in GMCs from post-first dose for nine serotypes but the percentage of participants with ≥4-fold-increase from baseline was similar post-second dose compared to post-first dose except for serotypes 6A and 19F. In children with kidney or lung diseases the immune responses after second vaccine dose were similar to post-first dose. Attenuated responses were observed for serotypes 3 and 19A in all study-groups, which was especially pronounced in the at-risk groups. CONCLUSION All study-groups mounted an immune response to PCV13, with the at-risk groups having responses that were mostly similar to the control children.

Hypertension as the trigger for posterior reversible encephalopathy syndrome in paediatric renal patients: An important diagnosis that should not be missed

BACKGROUND Posterior reversible encephalopathy syndrome (PRES) is a reversible neurological condition presenting with seizures and visual disturbances and diagnosed on magnetic resonance imaging (MRI). Little is understood about its pathogenesis, particularly in children, but it is thought to be related to hypertension. OBJECTIVES To review the presentation, diagnosis and outcome of PRES in paediatric renal patients at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa, between 1 January 2000 and 31 January 2017 and compare these with published case reports to date. METHODS This was a retrospective analysis of five new cases and a review of the existing literature. RESULTS The five reported patients were all hypertensive at the time of diagnosis and presented with seizures. Most (91%) of the 64 reviewed patients were also hypertensive at initial presentation. All five of the reported and 91% of the reviewed patients presented with seizures. The most common pattern of change on MRI occurred in the parietal and occipital regions. Complete neurological recovery occurred in four of the five reported and 87.5% of the reviewed patients. CONCLUSION All patients presented clinically with hypertensive crises and radiological evidence of PRES. Seizures were the most common presenting symptom. The prognosis for paediatric patients with PRES is favourable, so it is important to confirm the diagnosis in low-resource settings where intensive care is limited.

Emphysematous Pyelonephritis in Children

Emphysematous pyelonephritis is a severe necrotizing infection of the kidneys characterized by gas formation within the parenchyma, the collecting system or the perinephric tissue. To our knowledge, there have only been 4 cases of this condition reported in children. We report 2 additional cases in children managed at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.